This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Development of an effective vaccine or topical compound to prevent HIV transmission remains a major goal for control of the AIDS pandemic. Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a partially effective T-cell-based HIV vaccine. A significant delay in simian/human immunodeficiency virus (SHIV) acquisition (Log-rank test;p=0.0416) was seen only in vaccinated macaques that were repeatedly challenged in the presence of a microbicide comprised of an HIV nucleocapsid protein inhibitor. Peak acute viremia was lower (Mann-Whitney test;p=0.0387) and viral burden was also reduced (Mann-Whitney test;p=0.0252) in the combination-treated animals. These findings have implications for future development of HIV prevention strategies employing topical microbicides/pre-exposure prophylaxis (PrEP) and vaccines.